Non-linear partitioning and organic volatility distributions of urban aerosols.

Gas-to-particle partitioning of organic aerosols (OA) is represented in most models by Raoult's law, and depends on the existing mass of particles into which organic gases can dissolve. This raises the possibility of non-linear response of particle-phase OA mass to the emissions of precursor volatile organic compounds (VOCs) that contribute to this partitioning mass. Implications for air quality management are evident: a strong non-linear dependence would suggest that reductions in VOC emission would have a more-than-proportionate benefit in lowering ambient OA concentrations. Chamber measurements on simple VOC mixtures generally confirm the non-linear scaling between OA and VOCs, usually stated as a mass-dependence of the measured OA yields. However, for realistic ambient conditions including urban settings, no single component dominates the composition of the organic particles, and deviations from linearity are presumed to be small. Here we re-examine the linearity question using volatility spectra from several sources: (1) chamber studies of selected aerosols, (2) volatility inferred for aerosols sampled in two megacities, Mexico City and Paris, and (3) an explicit chemistry model (GECKO-A). These few available volatility distributions suggest that urban OA may be only slightly super-linear, with most values of the normalized sensitivity exponent in the range 1.1-1.3, also substantially lower than seen in chambers for some specific aerosols. The rather low exponents suggest that OA concentrations in megacities are not an inevitable convergence of non-linear effects, but can be addressed (much like in smaller urban areas) by proportionate reductions in emissions.

Renal function correlates of postnatal diuresis in preterm infants.

A characteristic pattern of fluid homeostasis occurs in the first week of life in many preterm infants. Initially, urine output is low independent of fluid intake, subsequently a diuresis occurs, and finally urine output begins to vary with intake. Renal clearance measurements were made during each of these three phases to elucidate the renal mechanisms involved. Periods during which the ratio of urine output to fluid intake was greater than or equal to 1 and urine output was greater than or equal to 3 mL/kg/h were defined as diuretic. Of 22 preterm infants studied from 12 to 120 hours of age, 17 had at least one period of diuresis. In these infants, urine output, fluid intake rate, output to intake ratio, glomerular filtration rate, and fractional sodium excretion were lowest at 12 to 24 hours of age. During diuresis, urine output tripled without a significant change in fluid intake so that output to intake increased to levels exceeding unity. Diuresis was associated with significant increases in glomerular filtration rate and fractional sodium excretion. By 108 to 120 hours of age, urine output decreased despite an increase in fluid intake. This was accompanied by a decrease in glomerular filtration rate. These results suggest that the initial antidiuretic phase is the result of a low fractional sodium excretion in the face of a low glomerular filtration rate. Subsequently, diuresis and natriuresis occur as a result of abrupt, nonmaturational increases in glomerular filtration rate and fractional sodium excretion. With cessation of diuresis, glomerular filtration rate and fractional sodium excretion decrease and water and electrolyte output begin to vary appropriately with intake.

Renal bicarbonate excretion in extremely low birth weight infants.

OBJECTIVE: To test the hypothesis that due to the immaturity of their kidneys extremely low birth weight infants lose large amounts of bicarbonate in their urine. METHODS: Urine and blood samples collected every 8 to 12 hours for the first 4 days of life from 22 preterm infants 23 to 29 weeks' gestation weighing 540 to 982 g at birth were prospectively studied. RESULTS: As described previously, three phases of fluid homeostasis were identified. The first phase (prediuresis) was a period of low urine output followed by a period of spontaneous diuresis/natriuresis (diuretic phase) and then by a phase when urine output varied according to fluid intake (postdiuresis). Sodium, potassium, chloride, and bicarbonate excretion rates and bicarbonate balance (bicarbonate or acetate infused minus bicarbonate excreted) were calculated for each of the three phases. Urinary excretion of sodium, potassium, chloride, and bicarbonate increased from the prediuretic to the diuretic phase and decreased from the diuretic to the postdiuretic phase. During the diuretic phase 88% of renal sodium excretion was accompanied by excretion of chloride. Bicarbonate balance was positive in all three fluid phases. Cumulative renal bicarbonate loss over the first 4 days of life was 1.9 +/- 0.5 meq/kg (SD) and the cumulative bicarbonate balance was +4.4 +/- 4.1 meq/kg (SD). The glomerular filtration rate, filtered load of bicarbonate, and absolute tubular reabsorption of bicarbonate significantly increased from the prediuretic to the diuretic phase, while fractional reabsorption of sodium and chloride decreased between these two phases. The fractional reabsorption of bicarbonate did not change from prediuresis to diuresis, but increased from diuresis to postdiuresis and consequently from prediuresis to postdiuresis. CONCLUSIONS: Contrary to our original hypothesis, the total renal bicarbonate excretion of extremely low birth weight infants in the first 4 days of life is low and the net bicarbonate balance is positive. The anion predominantly accompanying the excretion of sodium in all three phases is chloride and not bicarbonate. Bicarbonate excretion appears to be independent of sodium excretion during these phases. The increase in renal tubular bicarbonate reabsorption during the first week of life may be associated with extracellular volume contraction.

Phases of fluid and electrolyte homeostasis in the extremely low birth weight infant.

OBJECTIVE: We had shown previously that preterm infants undergo three phases of fluid and electrolyte homeostasis; prediuretic, diuretic, and postdiuretic. The objectives of the present study were: (1) to determine whether infants even more immature and infants cared for under thermal environmental conditions different from those previously studied also undergo these three phases; and (2) to relate these phases to changes in renal function. METHODS: Consecutive, timed urine collections were made during the first 5 days of life in 32 infants with birth weights of 1000 g or less. Infants were cared for in radiant warmers for 24 hours and then transferred to nonhumidified incubators. Diuresis was defined as urine flow rate (V) of 3 mL or more/kg per hour and weight loss of 0.8 g or more/kg per hour. The physiologic relationships among water and sodium balance, insensible water loss, arterial blood pressure, and renal function were made during the three phases. RESULTS: Twenty-eight (87%) of the 32 infants underwent the three homeostatic phases. The median ages of onset and cessation of diuresis were 25 and 96 hours, respectively. There was no correlation between onset of diuresis and change of thermal environment. During the prediuretic phase, V averaged 1.6 mL/kg per hour, and 17 of 28 infants had at least one collection period in which V was less than 1 mL/kg per hour; urinary sodium excretion was 0.1 mEq/kg per hour; the glomerular filtration rate (GFR) was 0.22 mL/kg per hour; fractional excretion of sodium (FENa) was 6.2%; and urine osmolality was dilute (221 mOsm/kg). During the diuretic phase, V and sodium excretion more than tripled; GFR and FENa doubled; and there was no change in urine osmolality. During postdiuresis, V and Na excretion decreased to values intermediate between the prediuretic and diuretic phases, and FENa fell to prediuretic levels, but there was no change in GFR or urine osmolality. There was poor correlation between blood pressure and GFR. Insensible water loss was high and variable during all phases, exceeding 190 mL/kg per day in the smallest infants. CONCLUSIONS: Extremely low birth weight infants manifest three phases of fluid and electrolyte homeostasis, as do more mature infants, independent of thermal environment. Diuresis and natriuresis are the result of abrupt increases in GFR and FENa. We speculate that this may be the result of expansion of the neonatal extracellular space as fetal lung fluid is reabsorbed.

Preservation of cerebral autoregulation in the unanesthetized hypoxemic newborn dog.

Studies were conducted to determine the effects of hypoxemia on cerebral blood flow and the influence of hyperoxia and hypoxemia on autoregulation of cerebral blood flow in the unanesthetized newborn dog. Twenty-one newborn dogs less than 2 weeks of age were studied. Cerebral blood flow was measured using radioactive microspheres during successive periods of normotension, hypotension (produced by blood withdrawal) and normotension (produced by infusion of previously withdrawn blood). In the hyperoxic animals, arterial pO2 was maintained above 250 torr by having the animal breathe 100% oxygen, while in the hypoxemic animals arterial pO2 was maintained between 30 and 35 torr by having the animal breathe 12% O2. Cerebral blood flow increased significantly with hypoxemia. In both hypoxemic and hyperoxic animals cerebral blood flow was maintained constant in spite of a large fall in arterial blood pressure and cardiac output, demonstrating the presence of autoregulation. Calculated oxygen transport to the brain was constant during hypoxemia and hypotension in all animals. Thus autoregulation of cerebral blood flow is present in newborn animals and is preserved under conditions of moderate hypoxemia.

The effect of metabolic acidosis upon autoregulation of cerebral blood flow in newborn dogs.

The radioactive microsphere technique was used in 13 newborn dogs to determine the effect of a metabolic (lactic)acidosis upon cardiac output (CO), cerebral blood flow (CBF), and autoregulation of cerebral blood flow. The animals were mechanically ventilated with supplemental oxygen to ensure normocarbia and hyperoxia throughout the experiments. Baseline cardiac output and cerebral blood flow measurements were made, followed by a lactic acid infusion to maintain pH less than 7.25. Metabolic acidosis produced a 27% fall in cardiac output and no change in cerebral blood flow (19 ml/100 g/min). Autoregulation was tested in 6 of the acidemic puppies by acute volume depletion to reduce blood pressure by 30% of baseline, followed by rapid volume re-expansion of the withdrawn blood. With volume depletion, CO decreased by 38%, and with volume re-expansion CO returned to baseline. The CBF remained at baseline levels with volume depletion but was slightly increased after rapid volume re-expansion. Five acidemic controls maintained CO and CBF constant with time. Thus cerebral autoregulation is preserved in the newborn dogs during metabolic acidosis, although cerebral blood flow was slightly increased following volume re-expansion.

Effects of Carbicarb and sodium bicarbonate on hypoxic lactic acidosis in newborn pigs.

BACKGROUND: Use of sodium bicarbonate (NaHCO3) may result in intracellular acidosis due to the generation of CO2. Carbicarb, has been reported to be superior to sodium bicarbonate (NaHCO3) because of lesser generation of CO2. The present study was designed to investigate whether Carbicarb or NaHCO3 is superior to normal saline in the treatment of hypoxic lactic acidosis. METHODS: Hypoxia was induced by ventilation with 8% O(2) in 30 piglets with fixed ventilation. When the pH fell to < 7.2, hypoxia was reversed by placing the animals in 21% O2 (experiment 1) or 100% O(2) (experiment 2) and either saline, Carbicarb or NaHCO3 were given. Data were collected for 120 minutes after therapy. RESULTS: In both experiment 1 (severe acidosis, pH < or = 7.1) and 2 (moderate acidosis, pH < or = 7.2) use of Carbicarb and NaHCO3 increased the arterial carbon dioxide tension (pCO2) significantly (p < 0.05). With moderate acidosis: 1) use of alkalinizing agents compared to saline resulted in an initial improvement in arterial pH at 1 minute, but thereafter, the differences were not statistically significant; and 2) there were no differences in hemodynamic variables and plasma lactic acid concentration between the three groups. CONCLUSIONS: The data demonstrate that 1) both Carbicarb and NaHCO3 significantly increase arterial pCO2; and 2) use of either alkalinizing agent in moderate acidosis does not alter the course of acidosis.

Renal bicarbonate reabsorption in the new-born dog.

1. Renal bicarbonate reabsorption was measured in thirty new-born dogs 2-27 days of age. Plasma bicarbonate was varied in the puppies by exchanging their blood with blood containing high levels of bicarbonate and low levels of chloride.2. The exchange transfusion resulted in increases of plasma pH, P(CO2) and bicarbonate in the puppies without changing plasma sodium and potassium or glomerular filtration rate (g.f.r.) and body weight.3. There was no tubular reabsorption maximum (T(m)) for bicarbonate and reabsorption values as high as 50 muequiv/ml. g.f.r. could be attained. No animals excreted bicarbonate at plasma levels below 25 mM and some animals had plasma bicarbonate threshold values in excess of 40 mM.4. Bicarbonate reabsorption increased as arterial P(CO2) rose (r = 0.62) but this was due to the rise of filtered bicarbonate since (a) there was no correlation between arterial P(CO2) and bicarbonate reabsorption when factored by filtered bicarbonate and (b) lowering arterial P(CO2) by mechanical hyperventilation did not reduce bicarbonate reabsorption corrected for filtered load.5. Inhibition of renal carbonic anhydrase by acetazolamide (50 mg/kg) resulted in an inhibition of bicarbonate reabsorption of only 4.5 muequiv/ml. g.f.r. (less than 20% of the total). Even with renal carbonic anhydrase inhibited, there was no bicarbonate T(m) and bicarbonate reabsorption values as high as 40 muequiv/ml. g.f.r. could be attained.6. There was good correlation (r = 0.82) between inhibition of sodium and bicarbonate reabsorption during renal carbonic anhydrase inhibition. However, with carbonic anhydrase inhibited, there was no correlation between arterial P(CO2) and bicarbonate reabsorption.7. These results demonstrate that tubular bicarbonate reabsorption mechanisms in the new-born dog are as efficient as those reported for the adult as long as body fluid and plasma sodium and potassium levels are carefully maintained.8. The results are also consistent with a bicarbonate reabsorptive mechanism explained either by direct ionic bicarbonate reabsorption or by hydrogen ion secretion with diffusion of carbonic acid.

Renal sodium reabsorption during saline loading and distal blockade in newborn dogs.

The ability of the proximal tubule to respond to saline expansion and varying filtered sodium loads was studied in 27 neonatal dogs aged 1-23 days. Sodium reabsorption beyond the proximal tubule was blocked with ethacrynic acid and chlorothiazide. When puppies received an intravenous load of 0.9% saline for 1.5 h, fractional sodium reabsorption averaged 0.985. After the addition of distal blockade to the saline infusion fractional Na reabsorption fell to 0.512. During distal blockade alone fractional Na reabsorption was 0.701, and after 1.5 h of saline expansion added to distal blockade fractional Na reabsorption fell to 0.493. Thus, there was a significant decrease in proximal tubular fractional Na reabsorption after saline expansion in neonatal dogs, and the high fractional Na reabsorption and low Na excretion during saline loading without distal blockade must be due to a large distal Na reabsorption. When filtered sodium load was varied by raising and lowering the glomerular filtration rate during distal blockade, there was excellent correlation between amount of filtered and reabsorbed sodium (r = 0.92). Thus, glomerulotubular balance exists in newborn dogs when there is no saline expansion.

Effect of diet on renal response to salt challenge in neonatal piglets.

In piglets 14-40 days of age, blood pressure and glomerular filtration rate increased significantly with age and were lower than those reported for adult pigs. There was no effect of dietary salt on the maturation of these parameters and on tubular sodium reabsorption, although the piglets on a low salt diet had lower inulin space than piglets receiving higher dietary salt. After the completion of a 24-hour salt challenge there was little evidence of sodium retention and there was no effect of previous dietary salt intake on sodium excretion. However, salt challenge resulted in higher blood pressure and elevated serum sodium only in piglets on a low sodium diet. These results suggest that in contrast to puppies and infants, the renal response to salt challenge is physiologically adequate in piglets at 14-40 days although glomerular function is still immature. Dietary salt history appears to have little effect on the degree of sodium excretion during salt challenge in this age range.

Studies in acid-base balance. I. Effect of alkali therapy in newborn dogs with mechanically fixed ventilation.

The effect of rapid or slow infusion of hypertonic sodium bicarbonate on acid-base balance and serum osmolality was studied in 36 acidotic newborn dogs. Respiratory acidosis and hypoxia were produced by mechanically fixed hypoventilation. One group of animals breathed 100% O2 to prevent hypoxemia. Rapid infusion of HCO3- in acidotic and hypoxic animals resulted in only a transient (1 minute) and small (0.05 pH units) elevation of arterial pH followed by a continuous fall, resulting in a lower pH and a worsened metabolic condition than in the nontreated controls. In nonhypoxic acidotic animals, rapid infusion of HCO3- had little effect on arterial pH. PaCO2 increased suddenly by 17 Torr in hypoxic and, by 13 Torr, in nonhypoxic animals. There was a concomitant fall in PaO2 (15 Torr). Serum osmolality rose rapidly after rapid infusion of HCO3-. Rapid infusion of hypertonic bicarbonate into an animal or infant whose ventilation is fixed thus results in a less than predicted elevation of arterial pH. PaCO2 rises, PaO2 falls, and serum osmolality rises. The net result may be a worsening rather than an improvement in the animals' metabolic state.

A respiratory venous chemoreceptor in the young puppy.

An extracorporeal venovenous shunt system utilizing a membrane oxygenator to alter venous blood gases was used to study the regulation of ventilation in 28 newborn and 4 adult dogs. There was no effect of the extracorporeal circuit per se (without the oxygenator in the system) on essential cardiovascular or respiratory function. When the puppies were placed on the extracorporeal circuit with the oxygenator in the system to effect changes in mixed venous blood gas composition there was a significant increase in venous P02 (Pv02), a decrease in venous Pco2 (Pvco2), a rise in venous pH (PHv), and a marked fall in minute ventilation (VE). There were no significant changes in cardiovascular function or arterial blood gases to account for the depression of ventilation. Acute changes in Pvo2 produced appropriate directional changes of VE under conditions where other arterial and venous blood gases were held constant. At a low Pvco2/Paco2 ratio, ventilation was depressed compared to those conditions with a high ratio. At any Pvc02/Paco2 ratio, ventilation could be depressed by raising the Pvo2. In adult animals ventilation could not be altered by changing venous blood gases. These experiments support the existence of a respiratory chemoreceptor sensitive to both PO2 and PCO2 in the prepulmonary or venous circulation of the newborn animal.

Renal response of the new-born dog to a saline load: the role of intrarenal blood flow distribution.

1. The renal response to an intravenous saline load was studied in thirty new-born mongrel dogs aged 1-30 days and in seven adult dogs.2. After the infusion of isotonic saline at a rate of 2.0 ml. min(-1) kg(-1) for 15 min and then at a rate of 0.5 ml. min(-1) kg(-1) for an additional 105 min, the puppies excreted a significantly smaller fraction of the infused sodium than did the adults (P < 0.01).3. Both puppies and adults increased their glomerular filtration rates after the saline load. However, adults excreted a larger fraction of their filtered sodium than did the puppies (P < 0.01).4. There was no correlation between age and the ability to respond to a saline load during the first month of life.5. Intrarenal blood flow distribution was measured by the radioactive microsphere technique. After saline infusion in the puppy there was an increase in outer cortical blood flow but inner cortical blood flow remained relatively constant. The result was a decrease in the ratio of inner to outer cortical blood flow (IC/OC ratio). In contrast the IC/OC ratio tended to increase in the adult dog after saline expansion.6. There was no correlation between the magnitude of change of sodium excretion and the change of intrarenal blood flow distribution in the puppy.7. These results confirm that the natriuretic response of the new-born dog kidney is less efficient than that of the adult dog. This is due primarily to the failure of the puppy kidney to decrease fractional sodium reabsorption. Although the new-born dog alters intrarenal blood flow distribution in response to saline loading this alteration does not appear to play a significant role in sodium excretion.

Relationship between glucose and sodium excretion in the new-born dog.

1. The relationship between renal glucose and sodium excretion was studied in thirty-three new-born dogs aged 1-14 days and in ten adult dogs.2. Glucose was infused into the animals at rates sufficient to produce an amount of filtered glucose at least 1.5 times the tubular transport of glucose (saturating glucose load). In both puppies and adults tubular glucose reabsorption at saturating glucose loads varied directly with the glomerular filtration rate (r = 0.54 and 0.73 respectively, P < 0.01 for both).3. In the puppy, as the fraction of filtered sodium excreted (C(Na)/C(In)) increased from 0.05 to 0.45, the ratio, renal tubular glucose transport divided by glomerular filtration rate at saturating glucose loads, (T(G)/GFR)(m), decreased from 3.7 to 1.7 mg/ml. (r = -0.75, P < 0.01). In the adult C(Na)/C(In) was below 0.08 in all experiments and (T(G)/GFR)(m) was within the 95% confidence limits predicted by regression analysis of the data from puppies. Although mean (T(G)/GFR)(m) was greater in the adult than in the puppy (P < 0.01), when puppies had C(Na)/C(In) similar to that for adults, they had (T(G)/GFR)(m) values equivalent to that for the adult.4. There was excellent correlation between glucose excretion and water excretion for both adult and new-born dogs (r = 0.93 and 0.87, respectively). However, for any glucose loss, water loss was greater in the puppy than in the adult (P < 0.01).5. During the control period total sodium excretion (per gram kidney) and C(Na)/C(In) were similar in the new-born and adult dog. However, during glucose loading, the puppies excreted more sodium and had a higher C(Na)/C(In) than did the adult, although glucose excretion was greater in the adult than in the puppy (P < 0.01 for all comparisons).6. Glomerular blood flow, as measured by radioactive microspheres, was redistributed towards inner cortical nephrons during glucose loading in the puppy. There was no such redistribution of glomerular blood flow in the adult.7. Sodium reabsorption beyond the proximal tubule was blocked with ethacrynic acid and chlorothiazide. In the puppy, the increase of C(Na)/C(In) following a glucose load was the same whether the glucose load followed control or distal blockade collections, suggesting that reductions of sodium reabsorption following a glucose load probably came from the proximal tubule. C(Na)/C(In) during glucose loading plus distal blockade was significantly (P < 0.01) higher in the puppy (0.598) than in the adult (0.280), indicating that glucose diuresis produced a greater inhibition of proximal tubular sodium reabsorption in the new-born than in the adult dog. These results support the hypothesis that the high sodium excretion rate during glucose diuresis in the new-born dogs appears to be due to the greater sensitivity of the neonatal proximal tubule to the osmotic effect of glucose. When presented with a glucose osmotic load the new-born dog diminishes net proximal sodium reabsorption more than does the adult and thus depresses tubular glucose reabsorption to a greater extent. The lower values of maximal glucose transport rates found in new-born animals may be related, therefore, to the higher fractional sodium excretion rates during glucose diuresis rather than to a diminished intrinsic glucose transport capacity in the new-born kidney.

Factors affecting the maturation of glomerular filtration rate and renal plasma flow in the new-born dog.

1. The maturation of glomerular filtration rate was studied by comparison of thirty-six new-born mongrel dogs aged 1-35 days with six adult dogs.2. Under mannitol diuresis, glomerular filtration rate (GFR) rose from 0.16 ml. min(-1).g kidney(-1) at 1 day of age to 0.34 ml. min(-1).g kidney(-1) at 1 month of age. Adult GFR averaged 0.68 ml. min(-1).g(-1). There was good correlation of GFR with arterial blood pressure (r = 0.76, P < 0.001). Part of the statistical correlation of GFR with blood pressure was found to be independent of the relationship between blood pressure and age.3. Acute increases or decreases in blood pressure resulted in parallel changes in GFR in the puppies. There was no change of GFR with change of blood pressure in adult dogs. Carotid artery clamping, independent of blood pressure changes, produced increased renal vascular resistance and decreased GFR in the pups.4. Renal plasma flow (RPF) increased from 0.70 ml. min(-1).g(-1) at 1 day of age to 1.80 ml. min(-1).g(-1) at 1 month and showed good correlation with blood pressure (r = 0.67, P < 0.001). Filtration fraction (GFR/RPF) and renal vascular resistance did not vary with age in the pup and were the same as those for the adult.5. These results support the hypothesis that maturation of GFR and RPF are closely related to maturation of arterial blood pressure in the mongrel dog. The factors other than blood pressure which also affect renal maturation in the dog still need to be more clearly defined.

Factors affecting the maturation of renal PAH extraction in the new-born dog.

1. The maturation of renal para-amino-hippurate extraction (E(PAH)) was studied in thirty-nine mongrel new-born dogs aged 2-29 days. E(PAH) was also measured in five adult dogs for comparison.2. There was no apparent change of PAH extraction during the first month of life but E(PAH) was lower in the puppy than in the adult. Under mannitol diuresis E(PAH) averaged 0.49 for the puppies and 0.83 for the adult dogs (P < 0.001). E(PAH) averaged 0.48 for the puppies under nondiuretic conditions, a value not significantly different from that observed during mannitol diuresis. There was no correlation of E(PAH) with mean arterial blood pressure.3. Inulin extraction (E(In)) remained constant during the first month of life and was the same in the new-born and adult dog suggesting that preglomerular shunting of plasma away from functioning nephrons was the same for both the puppy and adult dog.4. E(PAH) did not change in the puppy when plasma concentrations varied from trace (using [(3)H]PAH) to 0.25 mM indicating that excessive PAH load is not a factor in the low E(PAH) of the puppy.5. Diffusion of PAH from the red blood cell was excluded as an explanation for the low E(PAH) since diffusion was the same for both the adult and new-born dog.

Natriuretic effect of oxytocin on saline-expanded neonatal dogs.

The natriuretic effect of oxytocin was studied in 40 anesthetized newborn dogs 2-33 days of age. After saline expansion, puppies excreted only 2.86% of the filtered sodium (adult dogs undergoing similar volume expansion excrete about 65-8% of the filtered sodium). After oxytocin was infused in these saline-expanded puppies at 8 mU x kg-1 x h-1, fractional sodium excretion increased to 7.51%. Oxytocin had no natriuretic effect in nonexpanded puppies. In nonexpanded animals, when distal nephron function was blocked by a combination of ethacrynic acid, chlorothiazide, and amiloride, fractional sodium excretion averaged 31%. In contrast, distal nephron blockade in saline-expanded animals resulted in fractional sodium excretion of 55%. When oxytocin was infused in either saline-expanded or nonexpanded puppies undergoing distal nephron blockade, there was no increase in sodium excretion. These results support the following conclusions. In the newborn dog 1) the attenuated natriuretic response to saline expansion is related to increased reabsorption of sodium in the distal nephron; 2) an adult type of natriuretic response to saline expansion can be induced in puppies by infusion of oxytocin; and 3) oxytocin inhibits sodium reabsorption in the distal nephron.